Eukaryotic Cell doi:10.1128/EC.00062-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum
Long Cui,
Jun Miao,
Tetsuya Furuya,
Xinyi Li,
Xin-zhuan Su,
and
Liwang Cui*
Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
* To whom correspondence should be addressed. Email:
luc2{at}psu.edu.
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Abstract |
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Histone acetylation, regulated by the opposing actions of histone acetyltransferases (HATs) and deacetylases, is an important epigenetic mechanism in eukaryotic transcription. Although an acetyltransferase (PfGCN5) has been shown to preferentially acetylate histone H3 at K9 and K14 in Plasmodium falciparum, the scale of histone acetylation in the parasite genome and its role in transcriptional activation are essentially unknown. Here using chromatin immunoprecipitation and DNA microarray (ChIP-chip) we mapped the global distribution of PfGCN5, histone H3K9 acetylation (H3K9ac) and tri-methylation (H3K9m3) in the P. falciparum genome. While the chromosomal distributions of H3K9ac and PfGCN5 were similar, they are radically different from that of H3K9m3. In addition, there was a positive, despite weakly correlation between relative occupancy of H3K9ac on individual genes and the levels of gene expression, which was inversely proportional to the distance of array elements from the putative translational start codons. In contrast, H3K9m3 was negatively correlated with gene expression. Furthermore, detailed mapping of H3K9ac for selected genes using ChIP and real-time polymerase chain reaction in three erythrocytic stages detected stage-specific peak H3K9ac enrichment at the putative transcriptional initiation sites, corresponding to stage-specific expression of these genes. These data are consistent with H3K9ac and H3K9m3 as epigenetic markers of active and silent genes, respectively. We also showed that treatment with a PfGCN5 inhibitor led to reduced promoter H3K9ac and gene expression. Collectively, these results suggest that PfGCN5 is recruited to the promoter regions of genes to mediate histone acetylation and activate gene expression in P. falciparum.
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